HER-2 negative

Ribociclib-induced vitiligo-like depigmentation is an under-recognized adverse effect. Early recognition and multidisciplinary management are key to optimizing oncologic care without compromising therapeutic benefit.

For more advanced BC, care costs rise substantially, mainly due to systemic therapies and hospital-based care. The HER status at cancer presentation significantly impacts care costs across all cancer stages.

The FROC model could help identify the low Ki67 expression (≤ 5%) and prevent unnecessary chemotherapy.

No statistically significant differences in ORR were detected according to prior CDK4/6 inhibitor exposure, number of prior treatment lines, or study design; however, these findings should be interpreted cautiously given the limited number of studies and substantial heterogeneity. Within a continuously evolving treatment landscape, further prospective studies are warranted to better define the optimal positioning of SG.

PD-L1 CN loss was associated with lower OS, particularly in HR(+) and HER2(-) patients. This result revealed the prognostic value of PD-L1 CNV in Indonesian advanced BC who received primary systemic therapy.

CDK4/6 inhibitor-based neoadjuvant therapy results in meaningful tumour downstaging and biological subtype modulation in HR+/HER2- breast cancer. The frequent conversion from Luminal B to Luminal A and the marked suppression of Ki-67 support the cytostatic, differentiation-driven mechanism of CDK4/6 inhibition. Although pCR rates remain modest compared with chemotherapy, the consistent biological and morphological responses highlight this approach as a lower-toxicity alternative or complement to chemotherapy in selected patients. Prospective studies incorporating proliferative dynamics and nodal outcomes are warranted.

P2, N=143, Active, not recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: May 2027 --> Nov 2027 | Trial primary completion date: Jul 2026 --> Dec 2026

 Switching CDK4/6i and ET conferred a statistically significant improvement of PFS in patients with progression or recurrence on prior CDK4/6i-containing therapy. These findings underscore the variability in survival outcomes based on post-CDK4/6i therapy choices in HR+/HER2- MBC, with promising evidence for rechallenging strategies.

We report a case of metastatic CRC that achieved CR following second-line treatment with FOLFIRI plus ramucirumab after disease progression on first-line FOLFOX plus panitumumab therapy...In the present case, a watch-and-wait strategy was selected to prioritize organ preservation. Given the lack of consensus, further investigation is required to define the optimal strategy for patients achieving CR.

Histology showed poorly differentiated adenocarcinoma with signet-ring cells, while immunohistochemistry confirmed metastatic lobular breast carcinoma. This case highlights a previously unrecognized diffuse micronodular endoscopic pattern and the importance of targeted biopsies and immunohistochemistry to avoid misdiagnosis.

While PARG inhibition as a monotherapy showed limited efficacy, high-throughput screening of FDA-approved drugs revealed a synthetic lethal interaction between PARG inhibition and fluoropyrimidines, including 5-fluorouracil (5-FU)...In patient-derived xenograft models, PARG inhibition significantly enhanced the efficacy of both 5-FU and the oral prodrug capecitabine...Clinically, PARG and RAD51AP1 protein levels were strongly correlated in GC tissues, and their co-expression defined a subset of patients with the worst survival. Collectively, these findings identify a PARylation-ubiquitination switch regulated by PARG that stabilizes RAD51AP1 to enhance HR repair, unveiling the PARG-RAD51AP1 axis as a key determinant of fluoropyrimidine sensitivity and a biomarker-directed target for combination therapy in GC.

Phenotype-specific therapies are incorporated through simple pharmacodynamic surrogates: Paclitaxel chemotherapy acting primarily on HER2+ cells and Notch-pathway inhibition targeting HER2- cells...In contrast, simultaneous initiation suppresses both phenotypes more effectively and avoids strong rebound. These findings highlight the importance of ecological structure in therapy design and support simultaneous combination therapy followed by targeted maintenance.